Acetic acid, [2-[[(1,1-dimethylethoxy)carbonyl]amino]ethoxy]- (9CI)

White crystalline powder

To a mixture of ethyl 2-[2-(tert-butoxycarbonylamino)ethoxy]acetate (1.00 g, 4.04 mmol) in a mixed solvent of THF (10 mL) and H2O (5 mL) was added LiOH (193 mg, 8.09 mmol). The reaction mixture was stirred at 25 C. for 2 hours. On completion, the reaction mixture was acidified with HCl (1 N) until the pH=5-6, then the mixture was concentrated in vacuo to removed THF, and the residue was extracted with EA (5×10 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated in vacuo to give the title compound (886 mg, 99% yield) as light yellow gum. 1H NMR (400 MHz, DMSO-d6) delta 7.37 (s, 1H), 3.57 (s, 2H), 3.43-3.40 (m, 2H), 3.06 (q, J=5.2 Hz, 2H), 1.37 (s, 9H).(1) To a solution of 5-aminofluorescein (Compound 12a) (347 mg, 1 mmol)And compound 9a (257 mg, 1 mmol) in ethyl acetate was added DCC (247 mg, 1.2 mmol), After stirring at room temperature for one hour, The product compound 13a was obtained (408 mg, 71% purified yield)(1) To a solution of 7-aminocoumarin (Compound 8a) (322 mg, 2 mmol)And compound 9a (494 mg, 2 mmol) in ethyl acetate was added DCC (412 mg, 2 mmol), After stirring at room temperature for one hour, The product compound 10a was obtained by post columnation(585 mg, 75% purified yield)A 250 ml two-neck flask equipped with a magnetic stirring bar and inside thermometer was charged with 1.5 g of 5-(tert.-butoxycarbonylamino)-3-oxavaleric acid (Z4, 6.85 mmol). The flask was cooled to 0 C. by means of an ice-water bath and 80 ml of pre-cooled TFA were added. The reaction mixture was stirred for 1 h at 0 C. and the progress of the reaction monitored by TLC. The TFA was removed under reduced pressure until the weight remained constant. The yield was 0.94 g (quantitative yield+residual TFA). (1163) 1H-NMR: (MeOD, 200 MHz) delta=4.21 (s, 2H); 3.84-3.76 (m, 2H); 3.24-3.11 (m, 2H). (1164) TLC: (hexane/ethyl acetate 1:1) Rf=0.05.A 100 ml 2-neck flask equipped with a magnetic stirring bar and inside thermometer was loaded with bromoacetic acid (1.00 g, 7.19 mmol), N-Boc-ethanolamine (2.32 g, 14.39 mmol) and 25 ml of THF. The reaction mixture was cooled down to 0 C. by means of an ice-water bath. 0.863 mg (21.59 mmol) of sodium hydride (60% w/w in paraffin) were added, the cooling bath was removed and the reaction mixture stirred for 2 h at room temperature. The reaction was quenched by addition of 150 ml of water and the basic solution (pH 10) extracted three times with 100 ml of diethyl ether. The aqueous phase was acidified to pH 2 with 1 N hydrochloric acid and extracted three times with 100 ml of diethyl ether. The combined organic phases were washed with saturated sodium bicarbonate solution (2×50 ml) and brine (50 ml), dried over sodium sulphate and evaporated to dryness. The title compound (1.53 g, 6.98 mmol, 97%) was used without further purification. (1160) 1H-NMR: (CDCl3, 200 MHz) delta=10.18 (bs, 1H); 6.50+5.26 (bs, 1H, ); 4.13 (s, 2H), 3.68-3.57 (m, 2H); 3.42-3.27 (m, 2H); 1.45 (s, 9H). (1161) TLC: (hexane/ethyl acetate 1:1) Rf=0.20.Example 42 2-(2-Aminoethoxy)-N-[(1S, 9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10, 13-dioxo-2, 3, 9, 10, 13, 15-hexahydro-1H, 12H-benzo[de]pyrano[3', 4':6, 7]indolizino[1, 2-b]quinolin-1-yl]acetamide Process 1: Tert-butyl [2-(2-{[(1S, 9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10, 13-dioxo-2, 3, 9, 10, 13, 15-hexahydro-1H, 12H-benzo[de]pyrano[3', 4':6, 7]indolizino[1, 2-b]quinolin-1-yl]amino}-2-oxoethoxy)ethyl]carbamate Mesylate of the compound (4) (3.10 g, 5.47 mol) was reacted in the same manner as Process 1 of by using Example 5(2S)-l-[4-(2-{6-Amino-8-[(6-bromo-l, 3-benzodioxol-5-yl)sulfanyl]-9H-purin-9- yl}ethyl)piperidin-l-yl]-l-oxopropan-2-yl (2-aminoethoxy)acetate hydrochloride [0152] A mixture of tert-butyl N-(2-hydroxyethyl)carbamate (1.0 g, 6.20 mmol) and chloroacetic acid (0.59 g, 1.0 equiv.) in THF (30 mL) was added NaH (0.52 g, 2.10 equiv.) portion wise at 0C and then the reaction mixture was refluxed for 5 h. At the end of this period the reaction mixture was cooled room temperature, acidified with IN HCl (100 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with brine (50 mL), dried (Na2S04), filtered and the solvent was evaporated under reduced pressure to give 2-[2-(tert- butoxycarbonylamino)ethoxy]acetic acid as an oil (0.95 g, 70%). This material was sufficiently pure for the next step and it was used without further purification. The title compound was then prepared by the standard coupling method described for using (25)-l-[4-(2-{6-amino- 8-[(6-bromo- 1 , 3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl} ethyl)piperidin- 1 -yl]-2- hydroxypropan-l-one (1.0 g, 1.82 mmol) and 2- [2-(tert-butoxycarbonylamino)ethoxy] acetic acid (0.64 g, 1.6 equiv.) followed by Boc deprotection with 4M HCl in dioxane and isolated as a hydrochloride salt. 1H NMR (DMSO-d6) delta 8.51 (s, 1H), 8.04 (br s, 3H), 7.44 (s, 1H), 7.06 (d, J = 4.0 Hz, 1H), 6.14 (s, 2H), 5.44 (m, 1H), 4.27 (m, 5H), 3.85 (m, 1H), 3.71 (br s, 3H), 2.98 (br s, 3H), 1.81-0.94 (m, 10H). TOF LC-MS [M+H]+ 650.1351.Preparation 43 tert-butyl [2-(2-{[2-({5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-3-yl}oxy)ethyl]amino}-2-oxoethoxy)ethyl]carbamate The title compound was prepared by the general method described above for preparation 35, using

Molecular Weight:219.23
XLogP3:0.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:7
Exact Mass:219.11067264
Monoisotopic Mass:219.11067264
Topological Polar Surface Area:84.9
Heavy Atom Count:15
Complexity:221
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes